PMID- 23846804
OWN - NLM
STAT- MEDLINE
DCOM- 20131211
LR  - 20220310
IS  - 1533-4023 (Electronic)
IS  - 0160-2446 (Linking)
VI  - 62
IP  - 1
DP  - 2013 Jul
TI  - HMG-CoA reductase inhibitors, simvastatin and atorvastatin, downregulate 
      ABCG1-mediated cholesterol efflux in human macrophages.
PG  - 90-8
LID - 10.1097/FJC.0b013e3182927e7c [doi]
AB  - Recent studies showed that statins reduce ATP-binding cassette transporter A1 
      expression and ATP-binding cassette transporter A1-mediated cholesterol efflux in 
      macrophages, whereas the effect of statins on ATP-binding cassette transporter G1 
      (ABCG1), another important lipid transporter, is still unclear. Here, we 
      investigated the expression and functionality of ABCG1 on statins in 
      THP-1-derived macrophages and human peripheral blood mononuclear cells. 
      Simvastatin and atorvastatin were used in this study. Treatment with statins 
      significantly decreased ABCG1-mediated cholesterol efflux in human macrophages 
      (from 33.8% +/- 2.8% of control to 22.9% +/- 1.7% of 10 microM simvastatin or to 23.3% +/- 
      3.3% of 10 microM atorvastatin; P < 0.01, n = 4), whereas the protein expression of 
      ABCG1 remained unaltered on statins. Further analysis revealed that 2 major ABCG1 
      isoforms responded to statins differently. The expression of ABCG1-S, which 
      exhibited higher activity in cholesterol efflux than ABCG1-L, was significantly 
      decreased on statins compared with increased expression of ABCG1-L. The results 
      suggested that the proportion change of ABCG1 isoform expressions could 
      contribute to reduced ABCG1 functionality under treatment with statins. The 
      effects of statins on ABCG1 isoform expression and functionality were reversed by 
      low-dose liver X receptor agonist, TO-901317, indicating that statins' 
      downregulation of ABCG1 functionality was likely through liver X 
      receptor-dependent pathway. In conclusion, simvastatin and atorvastatin decreased 
      ABCG1-mediated cholesterol efflux in human macrophages without alteration of 
      total ABCG1 protein level. The proportion change of ABCG1 isoforms expressions 
      may be involved in the down-regulation of ABCG1 functionality by statins, which 
      provided a novel mechanism for the regulation of ABCG1 activity.
FAU - Wang, Wei
AU  - Wang W
AD  - Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy 
      of Medical Sciences and Peking Union Medical College, Beijing, China.
FAU - Song, Wei
AU  - Song W
FAU - Wang, Yu
AU  - Wang Y
FAU - Chen, Lianfeng
AU  - Chen L
FAU - Yan, Xiaowei
AU  - Yan X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (ABCG1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Heptanoic Acids)
RN  - 0 (Hydrocarbons, Fluorinated)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Indicators and Reagents)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Liver X Receptors)
RN  - 0 (Orphan Nuclear Receptors)
RN  - 0 (Pyrroles)
RN  - 0 (Sulfonamides)
RN  - 0 (T0901317)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - A0JWA85V8F (Atorvastatin)
RN  - AGG2FN16EV (Simvastatin)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1
MH  - ATP-Binding Cassette Transporters/*antagonists & inhibitors/physiology
MH  - Animals
MH  - Atorvastatin
MH  - Biotinylation
MH  - Blotting, Western
MH  - CHO Cells
MH  - Cell Separation
MH  - Cells, Cultured
MH  - Cholesterol/*metabolism
MH  - Cricetinae
MH  - Cricetulus
MH  - Down-Regulation/drug effects
MH  - Heptanoic Acids/*pharmacology
MH  - Humans
MH  - Hydrocarbons, Fluorinated/pharmacology
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology
MH  - Indicators and Reagents
MH  - Lipoproteins, LDL/metabolism
MH  - Liver X Receptors
MH  - Macrophages/drug effects/*metabolism
MH  - Orphan Nuclear Receptors/agonists
MH  - Plasmids
MH  - Pyrroles/*pharmacology
MH  - Real-Time Polymerase Chain Reaction
MH  - Simvastatin/*pharmacology
MH  - Sulfonamides/pharmacology
MH  - Transfection
EDAT- 2013/07/13 06:00
MHDA- 2013/12/16 06:00
CRDT- 2013/07/13 06:00
PHST- 2013/07/13 06:00 [entrez]
PHST- 2013/07/13 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
AID - 00005344-201307000-00013 [pii]
AID - 10.1097/FJC.0b013e3182927e7c [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 2013 Jul;62(1):90-8. doi: 10.1097/FJC.0b013e3182927e7c.